Cell Therapy in Patients With Chronic Ischemic Heart Disease Undergoing Cardiac Surgery

Phase 1

• Conditions: Old Myocardial Infarction; Chronic Myocardial Ischemia; Left Ventricular Dysfunction
• Interventions: Procedure: bone marrow mononuclear cells injection; Procedure: placebo intramyocardial injection

• Registration Number: NCT01267331
• Lead Sponsor: Chinese PLA General Hospital

Brief Summary

This prospective, randomized, placebo-controlled study was designed to assess the safety, feasibility and efficacy of intramyocardial injection of autologous bone marrow mononuclear cells in patients with severe, chronic ischemic disease scheduled to coronary artery bypass surgery.

Detailed Description

Severe ischemic heart disease remains a clinical challenge; many patients have undergone surgical myocardial revascularization procedures, but still remain symptomatic despite optimal medical therapy. Cell therapy with autologous bone marrow-derived cells (BMC) is a novel therapeutic strategy being tested for surgical treatment in patients with severe, chronic ischemic heart disease.

This research study is being performed to find out more information about the safety, feasibility, and efficacy of direct intramyocardial injection of autologous BMC on the myocardial perfusion and left ventricular function as an adjunctive therapy (compared to placebo) in patients undergoing coronary artery bypass surgery (CABG). The heart function evaluations will be performed by electrocardiogram, echocardiogram, and cMRI at baseline and during 6 months follow-up.

The secondary objective of this study is to assess the effect of intramyocardial injection of autologous BMC on functional class (angina/heart failure), global and cardiovascular mortality, and major adverse cardiac events after undergoing coronary artery bypass surgery.

Study Timeline

• Status Verified: 2010-12
• Study Start: 2010-12
• Study First Submitted: 2010-12-23
• Study First Submitted QC: 2010-12-27
• Study First Posted: 2010-12-28
• Last Update Submitted: 2011-01-11
• Last Update Posted: 2011-01-12
• Primary Completion: 2012-12
• Study Completion: 2013-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Age between 18 and 75 years.
2. Scheduled to undergo CABG.
3. At least 3 months since last episode of myocardial infarction.
4. Echocardiogram-assessed LVEF between 15 and 40% (Simpson's rule).
5. Abnormal wall motion of at least one segment due to prior myocardial infarction shown by echocardiography or left ventriculography.
6. Abnormal myocardial perfusion in infarcted area by SPECT.
7. Willingness to participate and ability to provide written informed consent.

Exclusion Criteria

1. Contraindications to magnetic resonance imaging.
2. Need for urgent or emergent revascularization.
3. Severe valvular heart disease.
4. Confirmed myocardial infarction within 14 days, and/or rising cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.
5. Prior cardiac surgery.
6. Stroke within 3 months prior to CABG.
7. Immunosuppressive medication (e.g. prednisone, cyclophosphamide, etanercept, etc.)
8. Severe chronic renal insufficiency (serum creatinine ≥ 200 mmol/dl or need for dialysis), liver disease, (diagnosis of cirrhosis, chronic hepatitis, or elevation of serum transaminases ≥3 times the upper limit of normal), cerebrovascular disease requiring concomitant carotid endarterectomy, peripheral arterial disease (claudication as the primary factor limiting activity), active non-dermatological malignancy requiring on-going treatment, or any other condition that would place the patient at increased risk for complications in the judgment of the attending cardiologist or cardiac surgeon
9. Hemoglobin less than 10g/dL, white blood cell count less than 4,000/mm3, absolute neutrophil count less than 1500/mm3
10. Active infection, with a temperature greater than 37.5°C within 48 hrs prior to surgery and an unexplained white blood cell count in excess of 10,000/mm3
11. Significant cognitive impairment.
12. Any condition associated with a life expectancy of less than 6 months.
13. Participation in other studies.
14. Positive laboratory test results for HIV, HBC, and HCV.
15. Pregnant woman.
16. Inability or unwillingness to provide written informed consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
stem cells injection	bone marrow mononuclear cells injection	Direct intramyocardial injection of autologous bone marrow mononuclear cells during CABG
palcebo intramyocardial injection	placebo intramyocardial injection	Direct intramyocardial injection of placebo containing saline and 5% human serum albumin during CABG.

Primary Outcome Measures

Name	Time	Method
major adverse cardiac events	6 months	Freedom from Major Adverse Cardiac Event: cardiac death, myocardial infarction, repeat coronary bypass grafting or percutaneous intervention of bypassed artery

Secondary Outcome Measures

Name	Time	Method
left ventricular function	6 months	Globlal function,regional myocardial perfusion and function assessed by magnetic resonance iamge and echocardiogram

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China